Methods for Treating Hydrocephalus

a hydrocephalus and treatment method technology, applied in the field of hydrocephalus treatment, can solve the problems of increased neuronal death and long-term complications, and increase in pressure and tissue damage, and achieve the effect of broad and significant impact and inhibiting transepithelial ion transpor

Inactive Publication Date: 2020-03-19
INDIANA UNIV RES & TECH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0014]In accordance with the present disclosure, methods have been discovered that surprisingly allow for inhibiting transepithelial ion transport related to TRPV4 agonist stimulation. The present disclosure has a broad and significant impact, as it allows for treating hydrocephalus in subjects.

Problems solved by technology

Hydrocephalus is the buildup of fluid (cerebrospinal fluid-CSF) within the ventricular system of the brain, sometimes referred to as “water on the brain.” This is a serious condition that leads to neuronal death and long-term complications.
In adults with hydrocephalus, the fused nature of the adult cranium results in increased pressure and tissue damage.

Method used

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  • Methods for Treating Hydrocephalus
  • Methods for Treating Hydrocephalus

Examples

Experimental program
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Effect test

example 1

[0041]In this Example, the effect of pre-administration of fluoxetine on TRPV4-stimulated ion transport response was analyzed.

[0042]In order to follow transepithelial ion movement, Ussing chamber electrophysiological techniques were used. The choroid plexus model is a high resistance, continuous cell line of porcine choroid plexus epithelial cells grown on permeable supports. Cultures to be used for electrophysiological analyses were grown in 6-well, Transwell filters for 10-12 days at which time the cultures developed a high transepithelial electrical resistance mimicking the in vivo situation. The cells were mounted on electrophysiological apparatuses for analysis of transepithelial ion flux in response to inhibitory or stimulatory reagents. Filters were excised, mounted in a Ussing chamber, and connected to a DVC-1000 Voltage / Current Clamp with voltage and current electrodes on either side of the membrane. Each half of the chamber contained a tapered fluid compartment with fittin...

example 2

[0046]In this Example, the effect of pre-administration of fluoxetine or norfluoxetine on TRPVA-stimulated ion transport response was analyzed.

[0047]The same methods were used in this Example as in Example 1. As shown in FIG. 3, when the cells were pre-treated with fluoxetine or norfluoxetine from time −10 to 0 minutes (depicted as white symbols and grey symbols, respectively), the GSK1016790A-stimulated (at 0 minutes) transepithelial potassium secretion in the direction of the CSF was completely inhibited (FIG. 3). Further, pre-treatment with fluoxetine or norfluoxetine blocked this increased permeability (FIG. 4).

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Abstract

Methods for inhibiting transepithelial ion transport, inhibiting hydrocephalic development, and for treating hydrocephalus are disclosed herein. The methods include administering a potassium channel inhibitor to the individual. In one particular embodiment, the individual is administered the calcium-activated potassium channel inhibitor, fluoxetine.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 62 / 438,174 filed on Dec. 22, 2016, which is hereby incorporated by reference in its entirety.BACKGROUND OF THE DISCLOSURE[0002]The present disclosure relates generally to treating hydrocephalus. More particularly, the present disclosure relates to methods for inhibiting transepithelial ion transport, methods for inhibiting hydrocephalic development, and methods for treating hydrocephalus by administering inhibitors of potassium channels, and in particular, calcium-activated potassium channels such as fluoxetine.[0003]Hydrocephalus is the buildup of fluid (cerebrospinal fluid-CSF) within the ventricular system of the brain, sometimes referred to as “water on the brain.” This is a serious condition that leads to neuronal death and long-term complications. CSF is produced by the choroid plexus (CP), which is an epithelial cell lined tuft of capillaries that project into the...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/138
CPCA61K31/138A61P25/00
Inventor BLAZER-YOST, BONNIE L.
Owner INDIANA UNIV RES & TECH CORP
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